The Duration of Signaling through CD40 Directs Biological Ability of Dendritic Cells to Induce Antitumor Immunity

Watanabe, Satoshi; Kagamu, Hiroshi; Yoshizawa, Hirohisa; Fujita, Nanae; Tanaka, Hiroshi; Tanaka, Junta; Gejyo, Fumitake

doi:10.4049/jimmunol.171.11.5828

Cited by 39 publications

(35 citation statements)

References 43 publications

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“…Either in the initiation phase or in the effector phase, different outcomes could be obtained by providing with CD40 stimulation and the duration of stimulation. Consistent with other report, 15 the usage of iDCs for the priming phase could provide significant advantages in anticancer immunotherapy. In this study, we fully utilized the dual biological characteristics of DCs, that is, iDCs have the highest engulfing function to uptake the tumor apoptotic bodies and iDCs undergoing maturation by stimulating of CD40L in the tumor micro environmental possess the highest migratory activity to be able to effectively activate specific antitumor CTL.…”

Section: Discussionsupporting

confidence: 77%

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Intratumoral administration of immature dendritic cells following the adenovirus vector encoding CD40 ligand elicits significant regression of established myeloma

Liu

Xia

et al. 2004

Cancer Gene Ther

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Our previous study showed that J558 myeloma cells engineered CD40L lost their tumorigenicity in syngeneic mice, and the inoculation of J558/CD40L tumor cells further led to the protective immunity against wild tumors. In the present study, we investigated whether the vaccine can exert more efficient antitumor immunity by combination with adenovirus mediated CD40L gene therapy and immature dendritic cells (iDCs). The results demonstrated that intratumoral administration of iDCs 2 days after AdVCD40L injection, not only significantly suppressed the tumor growth, but also eradiated the established tumors in 40% of the mice. The potent antitumor effect produced by the combination therapy correlated with high expression of MHC, costimulatory and Fas molecules on J558 cells, which was derived from CD40L transgene expression. In addition, transgene CD40L expression could dramatically induce J558 cell apoptosis. Effectively capturing apoptotic bodies by iDCs in vivo could induce DC maturation, prime tumor-specific CTLs and tend to Th1-type immune response. Finally, in vivo depletion experimentation suggested both CD4 þ and CD8 þ T cells were involved in mediating the antitumor immune responses of combined treatment of AdVCD40L and iDCs, with CD8 þ T cells being the major effector. These findings could be beneficial for designing strategies of DCs vaccine and CD40L for anticancer immunotherapy.

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Section: Discussionsupporting

confidence: 77%

“…However, the most suitable conditioning of DCs for anticancer immunotherapy is not entirely clear. Watanabe et al 15 found that iDCs could provide significant advantages in anticancer immunotherapy rather than mDCs due to their ability to prime T cells in secondary lymphoid organs through immobilized anti-CD40 antibody stimulation model in vitro.…”

mentioning

confidence: 99%

Intratumoral administration of immature dendritic cells following the adenovirus vector encoding CD40 ligand elicits significant regression of established myeloma

Liu

Xia

et al. 2004

Cancer Gene Ther

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“…5). Recently it was reported that the duration of stimulation through CD40 influences migratory activity in vivo (30). CCR7 expression was increased when DCs were stimulated with anti-CD40 for 3 h, whereas it was decreased when DCs were stimulated with anti-CD40 for 24 h. Because DCs have a chance to interact with T cells in vivo, migratory activity of DCs in vivo could be different from in vitro migratory activity.…”

Section: Discussionmentioning

confidence: 99%

AIMP1/p43 Protein Induces the Maturation of Bone Marrow-Derived Dendritic Cells with T Helper Type 1-Polarizing Ability

Kim

et al. 2008

The Journal of Immunology

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AIMP1 (ARS-interacting multifunctional protein 1), previously known as p43, was initially identified as a factor associated with a macromolecular tRNA synthetase complex. Recently, we demonstrated that AIMP1 is also secreted and acts as a novel pleiotropic cytokine. In this study, we investigated whether AIMP1 induces the activation and maturation of murine bone marrow-derived dendritic cells (DCs). AIMP1-treated DCs exhibited up-regulated expression of cell-surface molecules, including CD40, CD86, and MHC class II. Additionally, microarray analysis and RT-PCR determinations indicated that the expression of known DC maturation genes also increased significantly following treatment with AIMP1. Treatment of DCs with AIMP1 resulted in a significant increase in IL-12 production and Ag-presenting capability, and it also stimulated the proliferation of allogeneic T cells. Importantly, AIMP1-treated DCs induced activation of Ag-specific Th type 1 (Th1) cells in vitro and in vivo. AIMP1-stimulated DCs significantly enhanced the IFN-γ production of cocultured CD4+ T cells. Immunization of mice with keyhole limpet hemocyanin-pulsed AIMP1 DCs efficiently led to Ag-specific Th1 cell responses, as determined by flow cytometry and ELISA. The addition of a neutralizing anti-IL-12 mAb to the cell cultures that had been treated with AIMP1 resulted in the decreased production of IFN-γ, thereby indicating that AIMP1-stimulated DCs may enhance the Th1 response through increased production of IL-12 by APCs. Taken together, these results indicate that AIMP1 protein induces the maturation and activation of DCs, which skew the immune response toward a Th1 response.

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“…Our findings add to the existing knowledge that immobilized antibodies, such as those directed at CD3, 54 CD47, 55 or CD40, 56 display different biological ability on target cells from their soluble counterparts, and establish that ligation of CD22 by immobilized epratuzumab perturbs BCRmediated signals in malignant B cells without the involvement of anti-BCR antibodies. We also uncover, for the first time, a role of immobilized epratuzumab to stabilize F-actin and the potential of soluble epratuzumab to promote the adhesion of B cells to endothelial cells, which may occur in vivo to manifest the various biological activities observed for the immobilized epratuzumab in vitro.…”

Section: Discussionmentioning

confidence: 60%

Extensive crosslinking of CD22 by epratuzumab triggers BCR signaling and caspase-dependent apoptosis in human lymphoma cells

Chang

Wei

Gupta

et al. 2015

mAbs

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(2015) Extensive crosslinking of CD22 by epratuzumab triggers BCR signaling and caspase-dependent apoptosis in human lymphoma cells, mAbs, 7:1, 199-211, DOI: 10.4161/19420862.2014.979081 To link to this article: https://doi.org/10. 4161/19420862.2014 Abbreviations: Anti-IgM, F(ab') 2 fragment of affinity-purified goat anti-human IgM, Fc 5m fragment; BCR, B-cell antigen receptor; BSA, bovine serum albumin; CM-H 2 DCF-DA, 2 0 ,7 0 -dichlorodihydrofluorescein diacetate; Dc m , mitochondria membrane potential; DNP, 2,4-dinitrophenyl; EC, endothelial cells; ERKs, extracellular signal-regulated kinases; FBS, fetal bovine serum; FITC-DNase I, fluorescein isothiocyanate-conjugated DNase I; 488-annexin V, Alexa Fluor 488-conjugated annexin V; GAH, F(ab 0 ) 2 fragment of affinity-purified goat anti-human IgG Fcg fragment-specific; HUV-EC, human umbilical vein endothelial cells; ITIM, immunoreceptor tyrosine-based inhibition motif; JNKs, c-Jun N-terminal kinases; JP, jasplakinolide; LatB, latrunculin B; Lyn, Lck/Yes novel tyrosine kinase; MAP kinases, mitogen-activated protein kinases; mIgM, membrane IgM; MTS, (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; PARP, poly(ADP-ribose) polymerase; PBS, phosphate-buffered saline; PLCg2, phospholipase C, isotype gamma 2; Rhodamine-anti-IgG, rhodamine-conjugated F(ab 0 ) 2 fragment of affinity-purified goat anti-human IgG, F(ab 0 ) 2 fragment-specific; ROS, reactive oxygen species; 7-AAD, 7-aminoactinomycin D, Syk, spleen tyrosine kinase; TMRE/tetramethylrhodamine/ethyl ester Epratuzumab has demonstrated therapeutic activity in patients with non-Hodgkin lymphoma, acute lymphoblastic leukemia, systemic lupus erythematosus, and Sj€ ogren's syndrome, but its mechanism of affecting normal and malignant B cells remains incompletely understood. We reported previously that epratuzumab displayed in vitro cytotoxicity to CD22-expressing Burkitt lymphoma cell lines (Daudi and Ramos) only when immobilized on plates or combined with a crosslinking antibody plus a suboptimal amount of anti-IgM (1 mg/mL). Herein, we show that, in the absence of additional anti-IgM ligation, extensive crosslinking of CD22 by plate-immobilized epratuzumab induced intracellular changes in Daudi cells similar to ligating B-cell antigen receptor with a sufficiently high amount of anti-IgM (10 mg/mL). Specifically, either treatment led to phosphorylation of CD22, CD79a and CD79b, along with their translocation to lipid rafts, both of which were essential for effecting caspase-dependent apoptosis. Moreover, such immobilization induced stabilization of F-actin, phosphorylation of Lyn, ERKs and JNKs, generation of reactive oxygen species (ROS), decrease in mitochondria membrane potential (Dc m ), upregulation of pro-apoptotic Bax, and downregulation of anti-apoptotic Bcl-xl and Mcl-1. The physiological relevance of immobilized epratuzumab was implicated by noting that several of its in vitro effects, including apoptosis, drop in Dc m , and generation of ROS, could be obse...

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The Duration of Signaling through CD40 Directs Biological Ability of Dendritic Cells to Induce Antitumor Immunity

Cited by 39 publications

References 43 publications

Intratumoral administration of immature dendritic cells following the adenovirus vector encoding CD40 ligand elicits significant regression of established myeloma

Intratumoral administration of immature dendritic cells following the adenovirus vector encoding CD40 ligand elicits significant regression of established myeloma

AIMP1/p43 Protein Induces the Maturation of Bone Marrow-Derived Dendritic Cells with T Helper Type 1-Polarizing Ability

Extensive crosslinking of CD22 by epratuzumab triggers BCR signaling and caspase-dependent apoptosis in human lymphoma cells

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